A Synthetic Study of Biologically Active Compounds using Intramolecular Amidation

利用分子内酰胺化合成生物活性化合物的研究

• 批准号: 63570986
• 负责人: TAKAHATA Hiroki
• 金额: $ 0.32万
• 依托单位: Toyama Medical and Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570986/
• 关键词: Iodolactamization; Intramolecular Amidomercuration; Pyrrolidine; Unusual Amino Acids; Chiral Synthesis; Sharpless Asymmetric Oxidation; Asymmetric Induction; ヨードラクタミゼーション; チオアミド; アルカロイド; グルタミン酸; エポキシ化; ホモエノレート

Electrophilic olefin cyclization leading to carbon-heteroatom bonding is a very important process, particularly in the regio- and stereo- selective synthesis of heterocycles leading to biologically active compounds. We found an attractive iodine-induced lactamization on gamma,delta-and gamma,epsilon unsaturated thioimidates. Iodine-induced lactamization from gamma-unsturated thioimidates proceeds diastereo, regio(5-exo-trig)-, and stereo-selectively (1,2-cis- and 1,3-trans asymmetric induction), providing highly functionalized gamma-lactams, which are convertible into related biologically active compounds.Next, we found a intramolecular amidomercuration of N-delta, epsilon-unsaturated -gamma-hydroxyurethanes, giving cis-2-3-hydroxyuretnane. Interestingly, the Sharpless kinetic resolution of N-delta,epsilon-unsaturated-gamma-hydroxyalkenyl- urethanes provided optically active allylic alcohols and cis-3-hydroxy- 2-(hydroxymethyl)pyrrolidines. They were transformed into key synthetic intermediates for several biologically active compounds.

导致碳-杂原子键合的亲电烯烃环化是一个非常重要的过程，特别是在产生生物活性化合物的杂环的区域和立体选择性合成中。我们发现了γ，δ-和γ，ε不饱和硫代亚胺酸盐上有吸引力的碘诱导内酰胺化作用。碘诱导的γ-不饱和硫代亚胺酯内酰胺化可进行非对映、区域(5-exo-trig)-和立体选择性（1,2-顺式-和1,3-反式不对称诱导），提供高度功能化的γ-内酰胺，它们可转化为相关的生物活性化合物。接下来，我们发现了 N-δ、ε-不饱和-γ-羟基氨基甲酸酯的分子内酰胺汞化，给出顺式-2-3-羟基脲烷。有趣的是，N-δ,ε-不饱和-γ-羟基烯基-氨基甲酸酯的Sharpless动力学拆分提供了光学活性烯丙醇和顺式-3-羟基-2-(羟甲基)吡咯烷。它们被转化为几种生物活性化合物的关键合成中间体。

项目成果

高畑廣紀: 薬学研究の進歩. 5. (1989)

Hironori Takahata：药物研究进展5。（1989）

H.Takahata,T.Takamatsu,Y.-S.Chen,N.Ohkubo,T.Yamazaki,T.Momose,T.Date: "Electrophilic Olefin Heterocyclization in Organic Synthesis.Highly Stereoselective Synthesis of trans-3,5-Disubstituted Pyrrolidin-2-ones by Lodolactamization via Homoallylic Asymmetri

H.Takahata,T.Takamatsu,Y.-S.Chen,N.Ohkubo,T.Yamazaki,T.Momose,T.Date：“有机合成中的亲电烯烃杂环化。反式 3,5-二取代的高度立体选择性合成

H. Takahata, E. Ohkura, K. Ikuro, T. Yamazaki: "N-Benzyl-3-(tri-n-butylstannyl)propionthioamide as Thiohomoenolate Synthon. Synthesis of Some Heterocycles" Synthetic Communications 20, 285-292, 1990.

H. Takahata、E. Ohkura、K. Ikuro、T. Yamazaki：“N-Benzyl-3-(三正丁基甲锡烷基)丙硫酰胺作为硫代高烯醇盐合成子。一些杂环的合成”Synthetic Communications 20, 285-292, 1990。

H.Takahata,M.Tajima,Y.Banba,T.Momose: "Electrophilic Olefin Heterocyclization in Organic Syntesis.Intramolecular Amidomercuration of γ-Hydroxy-δ,ε-Unsaturated Urethanes" Chemical Pharmaceutical Bulletin. 37. 2550-2552 (1989)

H. Takahata、M. Tajima、Y. Banba、T. Momose：“有机合成中的亲电烯烃杂环化。γ-羟基-δ,ε-不饱和氨基甲酸酯的分子内酰胺化”化学制药通报 37. 2550-2552 (1989)。

高畑広紀: "チオアミド基の特性を活用する新規有機合成反応の開発" 薬学研究の進歩. 5. 35-45 (1989)

Hironori Takahata：“利用硫代酰胺基团的特性开发新的有机合成反应”《药物研究进展》5. 35-45 (1989)。